The twelfth annual symposium of the Breast and Tumor Center at the Inselspital Bern, which was held at the end of December 2013, focused this time on cervical carcinoma. What is the role of PET/CT in primary staging and follow-up, is it helpful or necessary? Furthermore, the occurrence of such carcinoma during pregnancy is a rare but challenging situation. Lastly, the role of chemotherapy and sentinel lymph node biopsy were also discussed.
According to Bernd Klaeser, MD, of the University Department of Nuclear Medicine at Inselspital Bern, PET/CT is the best imaging method available today for lymph node and distant metastasis staging in cervical cancer stage ≥IB1 (FIGO classification). “In the literature, sensitivity is described as 30-75% and specificity as >95%. At Inselspital, however, state-of-the-art equipment and special imaging techniques are now used to achieve better visualization, especially of small metastases less than 1 cm in size, which often escaped detection in the past. The detection rate of small lymph node metastases can thus be doubled,” Dr. Klaeser explained. The results of PET/CT have a direct impact on the treatment plan: A “clear” finding justifies radiochemotherapy. However, in the case of a suspicious finding, specific clarification, e.g., by means of laparoscopic lymph node sampling, is required. Distant metastases lead to a palliative therapy concept as in other tumors. “So in primary staging, PET/CT is necessary,” Dr. Klaeser concluded.
In follow-up and for recurrence diagnosis of cervical carcinoma, PET/CET is also the optimal imaging method. The literature indicates a sensitivity and specificity of ≥90%. As in primary staging, PET/CT results have a major therapeutic impact in about one-third of patients. PET/CT is used at Inselspital for verification of suspicious findings, prior to recurrence surgery and for therapy monitoring after radiochemotherapy. According to Dr. Klaeser, it is helpful and indicated when PET/CT results will potentially have an impact on treatment, but it is not mandatory in every patient.
The sentinel lymph node biopsy
What are the advantages and disadvantages of sentinel lymph node biopsy? This question was posed by Prof. Patrice Mathevet, MD, of CHUV Lausanne. “For breast, vulvar cancer and for melanoma showed:
- An excellent positive predictive value
- A detection of sentinel lymph nodes in unusual locations
- The identification of micrometastases when lymph nodes are subjected to serial sectioning and immunohistochemistry (IHC)
- A simple spontaneous assessment of nodal status,” Prof. Mathevet said. Moreover, compared with complete lymph node dissection, sentinel lymph node biopsy alone has a lower morbidity (Senticol-2 study).
Disadvantages include long operative time, risk of allergies, need for preoperative isotopic injection, and increased costs.
Cervical carcinoma in pregnancy
Prof. Dr. med. Wolfgang Schöll from the University Clinic for Gynecology in Bern discussed the significance of cervical carcinoma in pregnancy: “3% of these carcinomas are found in pregnant women. The median age in this case is 35 years. So the occurrence of this constellation is rare, but all the more difficult to address.” There are a variety of therapeutic options:
- A radical hysterectomy with fetus in situ or after a cesarean section.
- An abdominal or vaginal radical trachelectomy
- A conization with or without chemotherapy
- Laparoscopic staging with or without neoadjuvant chemotherapy followed by radical hysterectomy after cesarean section
- Neoadjuvant chemotherapy followed by cesarean section and radiochemotherapy or radical hysterectomy
- A prolongation of pregnancy until fetal maturity and the start of oncological therapy after delivery by cesarean section.
The majority of cervical carcinomas in pregnancy can be classified as IB according to FIGO, which is also the highest classification still allowed for pregnancy preservation. Other requirements include an explicitly expressed desire by the patient to keep the child, negative lymph nodes, and a diagnosis during the late second or early third trimester. Neoadjuvant chemotherapy, which aims to delay definitive oncologic therapy until the child is viable, appears to be a promising option. Cisplatin and paclitaxel (carboplatin) are used. However, a potentially harmful transfer to the fetus has not yet been conclusively discussed.
Conization, which is only considered at an earlier stage, brings complications such as bleeding, pregnancy loss or premature birth in 4-15%.
“Overall, occurrence during pregnancy has no negative impact on prognosis,” Prof. Schöll summarized.
Neoadjuvant, adjuvant and palliative chemotherapy
“Most women with early stages are cured after primary surgery or radiotherapy,” Manuela Rabaglio, MD, of the University Department of Medical Oncology at Inselspital, said of the role of chemotherapy in cervical cancer. “After primary surgery, radiotherapy in early stages with risk factors or positive lymph nodes may affect the risk of local recurrence but not distant metastasis. For stages IB-IIA, the risk of recurrence is lower when combined radiochemotherapy is used instead of radiotherapy alone.” Curatively, then, chemotherapy finds its way into treatment in conjunction with radiotherapy (neo-adjuvant, adjuvant). In a palliative approach, there is the option of monotherapy or as a two-drug combination.
Neo-adjuvant chemotherapy: neo-adjuvant chemotherapy before radical hysterectomy shows better results than hysterectomy alone in FIGO IB (“bulky”). This sequence is also superior to radical radiotherapy in FIGO IB2-IVA. Quick-VBP (vinblastine, bleomycin, cisplatin) and TIP (cisplatin, ifosfamide, paclitaxel) may be considered.
Adjuvant chemotherapy: adjuvant chemotherapy is used either concomitantly with radiotherapy and in stages IB-IIA. The active agent is then cisplatin 40 mg/m2 weekly during radiotherapy. Also showing good results is the use in combination with gemcitabine during and after radiotherapy [1].
Palliative chemotherapy: in the palliative setting (metastatic or recurrent cervical cancer), cisplatin and topotecan offers a survival advantage over cisplatin alone. The combination of bevacizumab plus cisplatin/paclitaxel or topotecan/paclitaxel (GOG 204) resulted in a survival advantage over chemotherapy in patients with chemotherapy-naïve recurrence or primary metastatic tumors.
“In summary, the (neo-)adjuvant chemotherapies lead to a reduction in the risk of recurrence or metastasis, and the palliative chemotherapies lead to an increase in life expectancy. However, the side effects and possible consequences for quality of life should not be underestimated,” Dr. Rabaglio concluded.
Source: 12th Symposium of the Breast and Tumor Center at Inselspital, December 19, 2013, Bern.
Literature:
- Dueñas-González A, et al: Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol 2011 May 1; 29(13): 1678-1685. doi: 10.1200/JCO.2009.25.9663. epub 2011 Mar 28.
InFo Oncology & Hematology 2014; 2(1): 35-36.
